Abstract

Protein-targeted therapies are expected to selectively kill tumor cells that express the targeted protein biomarker. Although a tumor mass may initially respond to targeted therapies based on expression of the targeted protein, all cells within a tumor may not express the targeted protein above a critical threshold level; therefore, those cells that do not express, or that downregulate expression of, the targeted protein may not be responsive to therapy. The ability to monitor the dynamic expression of these protein biomarkers throughout the course of therapy may allow for treatment to be personalized in real-time in response to the evolving nature of the tumor. This report demonstrates, by monitoring a single patient through multiple therapies, how targeted mass spectrometry is an effective, quantitative method that provides real-time analysis of multiple therapeutically associated targeted proteins that can be used to personalize a patient's treatment strategy throughout the course of care.

Conflict of interest statement

Drs. Sellappan, Blackler, Liao, Thyparambil, Cecchi, and Hembrough have disclosed that they are employed by and hold equity interest in NantOmics, LL. Dr. Catenacci has disclosed that he is on the advisory board for Genentech, Inc. The remaining author have disclosed that they have no financial interests, arrangements, affiliations, or commercial interests with the manufacturers of any products discussed in this article or their competitors.

Figures

Temporal assessment of (A) HER2, and (B) EGFR and HER3 protein expression in a patient with HER2-positive esophagogastric cancer treated with anti-HER2 therapy–containing regimens. Seven biopsies were collected over the course of treatment (x axis) and tested for HER2, EGFR, and HER3 protein levels measured in attomoles per microgram (amol/mcg; y axis). Treatments and their reported durations are shown in arrows. Continual treatment with anti-HER2 therapies resulted in decreased HER2 protein levels, whereas non-HER2 therapy (anti–programmed death-ligand 1 [PD-L1]) resulted in an increase in HER2 protein levels. The first 5 biopsies were from the primary tumor, and the last 2 biopsies were from progressing liver metastatic lesions. *A level of 750 amol/mcg of HER2 protein (gray horizontal line) correlates with HER2 gene amplification by FISH. ~Date of diagnosis. ^Date of death.

Figure 2

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CT analysis over treatment course…

Figure 2

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CT analysis over treatment course before and after the reintroduction of anti-HER2 therapy–containing…

Figure 2

CT analysis over treatment course before and after the reintroduction of anti-HER2 therapy–containing regimens. CT scans were taken over the course of treatment with anti-HER2 and anti– programmed death-ligand 1 (PD-L1) therapies. Multiple new liver lesions developed when anti-HER2 therapies were discontinued. Liver metastases regressed in number (smaller lesions were no longer visible), whereas larger lesions remain unchanged to slightly decreased in size) after anti-HER2 therapy was reintroduced.